The project consists of a series of clinical trials evaluating the clinical efficacy and safety of experimental therapeutic agents for the control of acute pain and perioperative apprehension in ambulatory patients undergoing minor surgical procedures. The surgical removal of impacted third molars serves as a model of minor surgery with associate pain and perioperative apprehension. All studies are double- blind with randomly allocated, parallel treatment groups and multiple dependent measures of therapeutic efficacy and clinical safety. A recent study evaluated the analgesic efficacy of the combination of ibuprofen and oxycodone to define an analgesic combination which results in additive analgesia for the management of pain not responsive to the use of a single agent such as ibuprofen and related drugs. The highest dose of oxycodone (10mg) resulted in additive analgesia in comparison to ibuprofen alone (400 mg) or ibuprofen plus lower doses of oxycodone. This dose also produced a high incidence of undesirable effects such as nausea, vomiting, and drowsiness which would limit its use in ambulatory patients. Demonstration of an additive effect for an opioid-non steroidal anti-inflammatory drug combination, however, provides a basis for the management of severe acute pain with an oral drug combination when alternative treatments have proven inadequate. A parallel study evaluated the efficacy of nonsteroidal anti- inflammatory drugs applied peripherally at the site of injury. A proprietary formulation of ketoprofen was administered directly into third molar extraction sites in comparison to a placebo formulation. Administration of a dose which was 20% of the normal systemic dose suppressed administration of the same dose at the extraction site to oral administration of the gel formulation to demonstrate that the analgesic activity is not due to a systemic effect following absorption from the extraction site. Replication of an analgesic effect would support peripheral administration for achieving greater efficacy and a lower incidence of side effects by minimizing systemic exposure. A previous study demonstrated that oral administration of a benzodiazepine hypnotic agent produces anxiolytic activity in th oral surgery model comparable to parenteral administration of diazepam. A current study is evaluating if sublingual administration of triazolam results in greater efficacy or less psychomotor effects than oral administration of the same dose. Preliminary results suggest that sublingual administration produces greater anxiety relief but without any greater psychomotor impairment than oral administration. These two studies hold promise for the clinical use of a single entity, non- parenteral form of sedation with efficacy comparable to parenteral administration but with greater safety.